title: Midbrain-hindbrain malformations in patients with malformations of cortical development and epilepsy: a series of 220 patients.
abstract: Midbrain-hindbrain malformations (MHM) may coexist with malformations of cortical development (MCD). This study represents a first attempt to investigate the spectrum of MHM in a large series of patients with MCD and epilepsy. We aimed to explore specific associations between MCD and MHM and to compare two groups of patients: MCD with MHM (wMHM) and MCD without MHM (w/oMHM) with regard to clinical and imaging features. Two hundred and twenty patients (116 women/104 men, median age 28 years, interquartile range 20-44 years at the time of assessment) with MCD and epilepsy were identified at the Departments of Neurology and Pediatrics, Innsbruck Medical University, Austria. All underwent high-resolution MRIs (1.5-T) between 01.01.2002 and 31.12.2011. Midbrain-hindbrain structures were visually assessed by three independent raters. MHM were seen in 17% (38/220) of patients. The rate of patients wMHM and w/oMHM differed significantly (p=0.004) in three categories of MCD (category I - to abnormal neuronal proliferation; category II - to abnormal neuronal migration; and category III - due to abnormal neuronal late migration/organization): MCD due to abnormal neuronal migration (31%) and organization (23%) were more commonly associated with MHM compared to those with MCD due to abnormal neuronal proliferation (9%). Extensive bilateral MCD were seen more often in patients wMHM compared to those w/oMHM (63% vs. 36%; p=0.004). In wMHM group compared to w/oMHM group there were higher rates of callosal dysgenesis (26% vs. 4%; p<0.001) and hippocampal abnormalities (52% vs. 27%; p<0.001). Patients wMHM were younger (median 25 years vs. 30 years; p=0.010) at the time of assessment and had seizure onset at an earlier age (median 5 years vs. 12 years; p=0.043) compared to those w/oMHM. Patients wMHM had higher rates of learning disability (71% vs. 38%; p<0.001), delayed developmental milestones (68% vs. 35%; p<0.001) and neurological deficits (66% vs. 47%; p=0.049) compared to those w/oMHM. The groups (wMHM and w/oMHM) did not differ in their response to antiepileptic treatment, seizure outcome, seizure types, EEG abnormalities and rate of status epilepticus. Presence of MHM in patients with MCD and epilepsy is associated with severe morphological and clinical phenotypes.
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, Innsbruck 6020, Austria.
authors.forename: Giorgi
authors.initials: G
authors.lastname: Kuchukhidze
authors.forename: Florian
authors.initials: F
authors.lastname: Koppelstaetter
authors.forename: Iris
authors.initials: I
authors.lastname: Unterberger
authors.forename: Judith
authors.initials: J
authors.lastname: Dobesberger
authors.forename: Gerald
authors.initials: G
authors.lastname: Walser
authors.forename: Julia
authors.initials: J
authors.lastname: Höfler
authors.forename: Laura
authors.initials: L
authors.lastname: Zamarian
authors.forename: Edda
authors.initials: E
authors.lastname: Haberlandt
authors.forename: Kevin
authors.initials: K
authors.lastname: Rostasy
authors.forename: Martin
authors.initials: M
authors.lastname: Ortler
authors.forename: Thomas
authors.initials: T
authors.lastname: Czech
authors.forename: Martha
authors.initials: M
authors.lastname: Feucht
authors.forename: Gerhard
authors.initials: G
authors.lastname: Bauer
authors.forename: Margarete
authors.initials: M
authors.lastname: Delazer
authors.forename: Stephan
authors.initials: S
authors.lastname: Felber
authors.forename: Eugen
authors.initials: E
authors.lastname: Trinka
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004827:Epilepsy / Q000209:etiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D054220:Malformations of Cortical Development / Q000150:complications* / Q000473:pathology*; D008636:Mesencephalon / Q000473:pathology*; D008875:Middle Aged; D012249:Rhombencephalon / Q000473:pathology*; D055815:Young Adult
keywords: Cortical dysplasia; Developmental disorders; Epilepsy; MRI; Midbrain–hindbrain